This research program has been constructed with the primary aim of investigating the controlling events concerned with differentiation, activation, and expression of biological function of various classes of specific immunocompetent lymphocytes. We intend to approach these issues by studying in depth the genetic events controlling these processes and the nature of the molecules concerned with specific recognition of thymus-derived or T lymphocyte function. The approach we intend to follow will focus on the role of gene products of the major histocompatibility complex (MHC) in the induction and control of somatic cell differentiation and the possible involvement of histocompatibility molecules in the recognition structures of immunocompetent lymphocytes. This approach is based on the accumulating evidence that certain MHC gene products exert biological activity which may be critical for cell activation and/or differentiation, in addition to perhaps forming an integral structural component of T cell receptors. These studies will be conducted in mice and will utilize new techniques for determining the controlling events of lymphocyte differentiation in vivo, and will also employ modifications of techniques establishd in other species for the induction and analysis of anti-idiotypic antisera that appear to react specifically with receptors on T lymphocytes. Such antisera, once developed in our hands, will be utilized to isolate, characterize and structurally analyze the T cell receptors in this species.